Masson Finds Molecules That Might Inhibit Key Enzyme in SARS-CoV-2 Replication

Three Ohio University chemists have found that molecules synthesized in their group might inhibit a key enzyme in SARS-CoV-2 coronavirus replication. Their work could potentially lead to the development of new antiviral drugs against SARS-CoV-2.

Dr. Eric Masson, post-doctoral associate Dr. Hector Barbero, and graduate student Nathan Thompson recently showed that Cucurbit[8]uril, a hollow pumpkin-shaped macrocycle, can secure a pair of Platinum-based molecules on top of each other—and can lead them to bind to any pair of sulfur-containing molecules. This study was recently published in the Journal of the American Chemical Society.

• See “Masson Co-Authors Paper in Top-Tier Chemistry Journal on Supramolecular Self-Sorting.”

In the meanwhile, Masson and Barbero showed that this pair of Platinum units also binds sulfur-containing cysteine residues on peptides to form large, yet well-defined peptide/metal/Cucurbituril assemblies.

Before the COVID-19 pandemic hit the world, Masson and Barbero had realized that their Cucurbituril-secured Platinum dimers would likely bind to proteins displaying a pair of cysteine residues close to each other, or to one cysteine residue and one neighboring amino acid prone to interactions with Platinum. But this hypothesis took a whole new turn when a few days ago, Masson discovered from an article in Chemical and Engineering News that the active site of a key enzyme needed for the replication of the SARS-CoV-2 coronavirus is a close pair of cysteine and histidine residues! As both amino acids can attach to Platinum, the active site of the dreadful enzyme, a cysteine protease, could be selectively targeted by the Platinum dimers designed by Masson and his co-worker.

Masson and Barbero are now designing a detailed research plan to quantify the binding properties of their Platinum dimers toward cysteine/histidine pairs, and to assess their inhibitory properties toward cysteine proteases.

As this work could potentially lead to the development of new antiviral drugs against SARS-CoV-2, Masson and Barbero are eagerly diving into this new challenge.